The long range goal of the present research is to develop chemical approaches to the study of biological membranes, their detailed chemical organization, dynamics and structure-function relationships. In studies of the outer membrane of Gram-negative bacteria, the structures of the lipo-polysaccharides, in particular lipid A, will be investigated. Chemical methods (crosslinking agents) will be developed for the study of interactions between different membrane components. As a model for lipid-lipid interactions, the interaction of the lipo- polysaccharide with phosphatidyl-ethanolamine will be studied. For studies of lipid-protein interactions, purified enzymes which have specific lipid requirements will be used together with the appropriate lipids. Reagents of varying size will be developed to label the membrane components on the surface or the interior as desired. In in vivo studies of the interacting membrane components, attempts will be made to introduce activated fatty acids into phospholipids using fatty acid requiring mutants. Membrane-DNA association will be investigated (a) by looking for a covalent linkage between DNA and a membrane component and (b) by attempting crosslinks between any proteins that may be involved and replicating DNA. Some of the proteins involved in in vivo DNA replications will thus be identified. $